Journal
CELL REPORTS
Volume 23, Issue 6, Pages 1665-1677Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.010
Keywords
-
Categories
Funding
- Ministerio de Economia y Competitividad (MINECO) [SAF2014-56894-R, SAF2015-63568-R]
- Fondation Jerome Lejeune
- Health and Science Departments of the Catalan Government (Generalitat de Catalunya) [2017SGR1080, 2014SGR633]
- Catalan Association for Rett Syndrome
- Spanish Association for Rett Syndrome
- European Community [PITN-GA-2009-238242-DISCHROM]
Ask authors/readers for more resources
Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG- binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels. In vivo, inhibition of Gsk3b prolongs the lifespan of Mecp2-KO mice and reduces motor deficits. At the molecular level, SB216763 rescues dendritic networks and spine density, while inducing changes in the properties of excitatory synapses. Gsk3b inhibition can also decrease the nuclear activity of the Nfkb1 pathway and neuroinflammation. Altogether, our findings indicate that Mecp2 deficiency in the RTT mouse model is partially rescued following treatment with SB216763.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available